Re-Print- Artificial Respiration in Severe COVID-19 Cases: A Beneficial or Deleterious Treatment

Research Article | DOI: https://doi.org/10.31579/2637-8876/017

Re-Print- Artificial Respiration in Severe COVID-19 Cases: A Beneficial or Deleterious Treatment

  • Kurt E. Müller 1*

1 Dresden International University (DIU). Dresden, Germany

*Corresponding Author: Kurt E. Müller, Dresden International University (DIU). Dresden, Germany.

Citation: Kurt E. Müller. (2021) Re-Print- Artificial Respiration in Severe COVID-19 Cases: A Beneficial or Deleterious Treatment, J. Immunology and Inflammation Diseases Therapy. 4(1); Doi:10.31579/2637-8876/017

Copyright: © 2021 Kurt E. Müller. This is an open-access article distributed under the terms of The Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Received: 02 August 2021 | Accepted: 10 September 2021 | Published: 20 September 2021

Keywords: SARS-CoV-2; COVID-19; artificial respiration; superoxide; oxidative shielding; oxidative stress; oxidative burst; hemofiltration

Abstract

The world over artificial respiration is employed as one of the intensive care treatment measures in severe cases of COVID-19 because of the significant respiratory distress patients develop. Nevertheless, the outcome is poor. Lethality varies from country to country and clinic to clinic between 50% and 90%. So the question arises as to whether the use of oxygen can be a risk factor in the treatment of acute inflammatory diseases in general and of COVID-19 in particular. Oxidative stress is the first and oldest step of cellular defense and starts before the activation of the immune system. This leads to an increase of intracellular oxygen in the mitochondria, followed by an elevated electron flow and the formation of superoxide as well as other reactive oxygen species and reactive nitrogen species. Superoxide reacts with nitric oxide, which is always present in inflammation, forming peroxynitrite, the strongest inducer of oxidative stress. This step induces the activation of nuclear factor kB, followed by the production of proinflammatory cytokines. The elevated levels of inducible nitric oxide synthase keep this cycle running. High amounts of superoxide have to be compensated and catabolized by manganese-superoxide dismutase 2 into hydrogen peroxide and in a second step by catalase into water. When using artificial respiration, these steps are accelerated considerably in the inflamed tissue of the lung, leading to a significant increase of the electron flow as well as an elevation of superoxide, oxidative stress, and water. As SARS-CoV-2 generally induces the production of proteins (and not only those necessary for viral reproduction), the water will remain in the tissue, causing edema and thus a wet lung syndrome associated with a growing oxygen diffusion distance to red blood cells. Ultimately, patients do not suffocate in spite of, but because of, the presence of high levels of oxygen. The limited number of patients who survive this deleterious treatment describe it as having had a sensation of drowning. The reasons will be discussed.

1. Introduction

Energy metabolism and defense mechanisms developed in parallel in evolution. Their interaction is essential for each of them to function properly.  In the beginning, 3.5 billion years ago, the process was anaerobic. In the oldest bacteria known, adenosine triphosphate (ATP) was produced by anoxygenic photosynthesis [1, 2] Oxygen was toxic. But substances and cellular mechanisms of the intermediary metabolism already existed in that past and are still utilized today. These are substances and mechanisms such as glycolysis, glyoxylate and the Krebs cycle, pyruvate dehydrogenase, the pentose phosphate pathway, the synthesis and oxidation of fatty acids, cobalamin, carotenoid and heme synthesis, iron-sulfur cluster synthesis, cytochromes (extremely relevant for drug metabolism), isoprenyl and ubiquinone synthesis and its interaction with the electron transport necessary for the defense mechanisms and proton coupling for ATP synthesis [3].

Almost one billion years later, oxygen became important. Cyanobacteria started producing oxygen in such quantities that the oxygen level in the atmosphere increased to 2-4% which allowed bacteria and viruses to leave the water of the oceans and populate the earth [1]. Mitochondria coordinated both energy production and defense mechanisms. They even organized the innate immune system necessary for the identification of targets for the activation of defense mechanisms [4]. The rising levels of oxygen in the environment facilitated an increased production of energy and promoted oxidative shield mechanisms. More energy production in turn means higher risk due to an increase in the number of electrons which form together with oxygen superoxide anions. At first these oxygen superoxide anions can be catabolized by manganese-superoxide dismutase 2 (Mn-SOD2) to hydrogen peroxide (H2O2), which is still an oxygen radical, and subsequently H2O2 is catabolized to water. In parallel, superoxide reacts with nitric oxide to form peroxynitrite, the most active substance in the development of oxidative stress by reactive oxygen species (ROS) and reaczive nitrogen species (RNS) [5].   

2. Regulation of defense

2.1 Mitochondria

The proteome of the mitochondrion contains almost 1500 proteins [6]. Two thirds of these have an enzymatic function, highlighting the enormous metabolic activity of these organelles. Under physiological conditions, the concentration of thousands of nutrients and metabolic substrates is strictly controlled by collective kinetic constants. Consequently, the whole system is mismanaged if even one of these is upregulated or downregulated for a longer period of time. Viral and microbial infections, changes in the natural environment, toxins, nutritional dysbalance, and medical treatment can thus cause a mismatch between the optimum and the actually existing concentration of metabolic substrates for the tissue [7]. This point will be of particular interest regarding severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). 

Most of the ATP in humans is generated by the combined action of the Krebs cycle and oxidative phosphorylation. Oxidative phosphorylation requires an electron transport chain, molecular oxygen, and ATP synthase located within the inner membrane of the mitochondria [8].  The reactions of the Krebs cycle produce reduced nicotinamide adenine dinucleotide (NADH) and reduced flavin adenine dinucleotide (FADH2). Both are electron donors for the electron transport chain that passes them sequentially to O2 to generate energy and to form water. The mitochondrion also contains the enzymes responsible for ß-oxidation of fatty acids to NADH and FADH2. Those reductants are located in the center of the mitochondrion and readily react with the electron transport chain. The exergonic reactions of the electron transport chain provide energy for the translocation of protons (H+) from the mitochondrial matrix through the inner mitochondrial membrane to the exterior.  Most of the oxygen consumed by humans is metabolized within the mitochondria. The driving force of mitochondrial function is a voltage difference (ΔΕ) between O2 and NADH (Figure. 1).

Figure 1: The voltage difference between O2 and NADH is the driving force of the mitochondrion.

The respiratory electron transport chain consists of four independent complexes (I, II, III, and IV). Coenzyme Q (CoQ) transports the electrons from complexes I and II to complex III, cytochrome c from complex III to IV. NADH donates its electrons to complex I. From there electrons are transferred to CoQ to form QH2, which passes its electrons on to complex III. A proton translocation reaction is needed to provide the energy. Complex II (succinate dehydrogenase) transports electrons without providing energy for proton translocation or ATP formation [8,9,10]. The major sources of physiological oxygen radicals which are natural by-products of oxidative phosphorylation can be found between complex I and CoQ and between CoQ and complex III (Figure. 2). 

Figure 2: Consequence of artificial respiration (oxygen) in COVID-19: extremely elevated electron flow and superoxide formation (red arrow) followed by excessive oxidative stress and elevated levels of H2O which remain in the tissue because of high protein synthesis caused by SARS-CoV-2.

They account for about 1% of the total oxygen uptake. This situation changes completely during artificial respiration as an elevated level of electrons and O2 form high amounts and ultimately uncontrollably high amounts of superoxide anions reacting with nitric oxide to form peroxynitrate, which in turn forms free radicals and induces oxidative stress [5]. Mitochondrial DNA is 15 times more sensitive to oxidative damage than nuclear DNA [11]. 

The physiological process of ATP production is also the dominant source of ROS and consequently of oxidative stress. Oxygen is an element urgently needed but also an element causing risks when activated to form singlet oxygen (¹O2) by means of energy transfer or by electron transfer forming superoxide anion radicals (•O2‾) [10]. As long as ROS remain compensated in a homeostatic and physiological reaction or are used for controlled defense for a limited period of time, deleterious effects can be avoided. The most important enzymes to act on •O2‾ are superoxide dismutases (SODs) which exist in three forms: Mn-SOD2) in mitochondria as well as copper-zinc superoxide dismutase (Cu/Zn-SOD2) in cytosol membranes.

2.2 Superoxide 

There are several metabolic steps leading to the production of superoxide. The most important in this context is the electron transport chain in the mitochondrion during ATP generation. Superoxide exists in two interconvertible forms. The more important one has an unpaired electron and a negative charge (٠O2‾ ),  the other one is an acid (٠OH). The negative charge keeps superoxide in the cells where it serves as an intracellular signaling molecule. Higher levels are damaging to cells. Therefore enzymes, (SODs) are needed to degrade superoxide. They can be found in all organisms dependent on the presence of oxygen in the air [10]. There are three forms: the first form is involved in the energy metabolism of the mitochondria, the second one can be found in the cytoplasm of cells, and the third one outside of cells. Each SOD is encoded by its own gene and has a distinct structure. Superoxide is metabolized by Mn-SOD2 to H2O2. Both ٠O2‾ and H2O2 have low reactivity. In the presence of transition metals, however they develop high amounts of ROS. 

2.3 Reactive Nitrogen Species 

RNS include nitric oxide (NO٠) and nitrogen dioxide (٠NO‾2), both of which are free radicals, and peroxynitrite (ONOO‾), a nonradical. They all have high oxidizing potential. The toxic effect of these molecules is referred to as “nitrosative stress” [12, 13]. They are also classified as ROS and summarized as reactive oxygen and nitrogen species (RONS). ٠NO is a relatively stable free radical with a half-life of 1 s. It is produced by oxidation of L-arginine to L-citrulline by the enzyme nitric oxide synthase (NOS) which takes three forms: inducible NOS (iNOS), endothelial NOS (eNOS), and neuronal NOS (nNOS) [14, 15]. NO٠ is a soluble lipid that can diffuse through membranes and is thus critically important in neurogenic membranes containing a different structural correlation of lipids and proteins [16]. 

NO٠ has both physiological and pathophysiological properties [17]. Because of its regulatory function it is considered a cytokine, in spite of the fact that it is structurally not identical to cytokines [18]. It causes vasodilation to regulate blood flow and consequently directs immune cells towards the site of inflammation. It also activates natural killer cells (NK cells). This positive effect is blocked when high levels of superoxide activate NO٠ and ٠O‾2 to form ONOO‾, a highly potent inducer of oxidative stress. This is the strongest inducer of oxidative stress and switch for the activation of nuclear factor-kB (NF-kB), which in turn triggers the production of proinflammatory cytokines (Figure. 3). 

Figure 3: The compounds nitric oxide, superoxide, and peroxynitrite as regulatory substances of the innate immune system and the role of nitric oxide synthase inducing a vicious cycle.

The blocking effect of OONO‾ acts more strongly on NK cells than the promoting effect of NO٠ [20, 21]. ONOO‾ can cause DNA fragmentation, lipid and protein oxidation, as well as nitration [22, 23].  

. SARS-CoV-2: from protection to damage

All coronaviruses have the highest affinity for the respiratory tract among all organs and functional systems. Generally the inflammation involves the pharynx, trachea, bronchi, and bronchioli. However, in coronavirus infectious disease-19 (COVID-19) the inflammation often extends to the entire pulmonary tissue corresponding to an enormous expansion of the inflamed area. This provokes a strong antioxidative defense reaction by the activation of the NO/٠O2‾ /ONOO‾ cascade followed by the upregulation of proinflammatory cytokines such as IFN y, IL 1, IL 6, IL 8, TNF α and others by activating NF-kB and the sympathetic nervous system, which also interacts with the immune cells. This cascade is controlled by SODs, glutathione peroxidase (GPx), catalase, Treg cells, IL 10, cortisol, and the parasympathetic nervous system [24] The mitochondria are the regulators of those mechanisms. As shown before, the voltage difference between O2 and NADH (ΔΕ) is the driving force. The uptake of even physiological amounts of oxygen by artificial respiration with compressed air in particular will deregulate and escalate the whole process of inflammation. The more oxygen is used, the higher the production of electrons and consequently of superoxide will be. It is less reactive in physiological concentrations. It becomes very reactive however, if a high quantity is formed, producing ٠ONOO‾ by reacting with ٠NO. The oxidative and nitrosative stress may become so acute that it results in an oxidative burst which in turn leads to damage of granulocytes, especially neutrophils, and macrophages breaking down cellular defense mechanisms () [10].

Figure 4: Normal mitochondrial function (1). Upregulation of mitochondrial function by uncontrollable oxidative stress and immune activation due to oxygen (2).

This may damage the sensitive mitochondrial DNA and immediately influence mitochondrial function. It has been demonstrated that the therapeutic treatment of various diseases with oxygen increased mortality without improving other patient-relevant outcomes [25]. The authors published a meta-analysis of 25 randomized studies with 16,037 patients treated with low and high-rate artificial respiration for various indications. Mortality was higher in all cases treated with high O2 flow than in the groups suffering from the same disease but treated with low levels of oxygen. In artificial treatment of COVID-19 patients, the oxygen reaches the inflamed tissue directly and is not distributed or attenuated through the blood stream. Therefore, its effect in COVID-19 is far more pronounced than in the cases referred to in the studies. A leakage of superoxide develops between complex I and CoQ and complex III, depending on the quantity and properties of CoQ. The overload of superoxide leads to an even stronger activation of inflammation by the vicious NO/ONOO‾ cascade and at the same increases the production of H2O2 and ultimately H2O by SOD and catalase. Latest findings demonstrate that SARS-CoV-2 in contrast to other coronaviruses  does not only lead to elevated protein synthesis for viral reduplication but higher levels of protein synthesis in general [26]. This increased production of proteins is an important factor for H2O accumulation in the tissue causing a wet lung syndrome associated with the sensation of drowning. The same group showed that cholesterol levels are lowered, which inevitably leads to a reduced synthesis of sex hormones and steroid hormones. As a result, the anti-inflammatory effect of cortisol is blocked. The effect can be even more pronounced in patients who had been treated with statins. Additionally, statins can also lead to an increased NO٠ level. Consequently, insulin resistance can be expected. It always develops in acute inflammation due to an increase in circulating glucose and free fatty acids which are no longer absorbed by the adipose tissue, liver, or muscles in order to provide energy for the central nervous system and the immune system [24, 27]. 

Environmental factors influence the extent of oxidative stress. Transition metals with atomic numbers 21-30, 39-48, 57-80, and 89-112 are electron donors and catalyze the formation of superoxide and free radicals. It is also one of the reasons why COVID-19 takes a more severe course in pe, itople in polluted regions like China, Lombardy, and large cities all over the world. Furthermore also is one the contributing factors for the severe clinical course in elderly patients as their total body burden is generally higher. Metals are also inducers of cell adhesion molecules on the surface of the endothelium [28]. They are catalyzers of superoxide but may as well increase the risk of thromboembolic processes often seen in COVID-19 patients. It has been shown just recently that nitrogen dioxid (NO2) levels are a contributing factor to COVID-19 fatality [29]. The antioxidative capacity depends on the quality and quantity of micronutrients. The presence of CoQ might be particularly important. Although there is no current data on this aspect for COVID-19 as yet, it is a well-known fact that a mismatch of micronutrients causes mitochondrial dysfunction [7]. 

4. Conclusion

Oxygen is a promoter of oxidative stress as a defense reaction and as an activator of the innate immune system. As long as these reactions stay under control, the required shielding effect is guaranteed, but high levels of oxygen render them uncontrollable. Artificial respiration increases this risk considerably within a short period of time. So what could be the solution? In patients showing signs of oxidative and nitrosative stress spiraling out of control, high dosages of substances of the cellular antioxidant defense system should be administered, such as vitamin C and E, reduced glutathione, taurine, cysteine, methionine, s-adenosyl-L-methionine, melatonin, selenium, and polyamines [30]. They should be combined with anti-inflammatory substances and drugs. Ivermectin has antioxidative and anti-inflammatory properties and also blocks mRNA of COVID-19 [31]. In severe cases, corticosteroids should be taken into consideration in spite of the viremia. In case of symptoms of wet lung disease, hemofiltration should be started immediately to extract the fluid from the blood and consequently from the lung via osmotic pressure. This should alleviate the sensation of drowning within 2 to 3 hours. Additionally, a therapeutic concept to avoid pulmonary fibrosis is required until the radiograph has normalized.

Affiliations

Dresden International University (DIU). Dresden, Germany. Feilbergstrasse 32.

Conflict of interests

The author declares that he has no competing interest.

References

Clearly Auctoresonline and particularly Psychology and Mental Health Care Journal is dedicated to improving health care services for individuals and populations. The editorial boards' ability to efficiently recognize and share the global importance of health literacy with a variety of stakeholders. Auctoresonline publishing platform can be used to facilitate of optimal client-based services and should be added to health care professionals' repertoire of evidence-based health care resources.

img

Virginia E. Koenig

Journal of Clinical Cardiology and Cardiovascular Intervention The submission and review process was adequate. However I think that the publication total value should have been enlightened in early fases. Thank you for all.

img

Delcio G Silva Junior

Journal of Women Health Care and Issues By the present mail, I want to say thank to you and tour colleagues for facilitating my published article. Specially thank you for the peer review process, support from the editorial office. I appreciate positively the quality of your journal.

img

Ziemlé Clément Méda

Journal of Clinical Research and Reports I would be very delighted to submit my testimonial regarding the reviewer board and the editorial office. The reviewer board were accurate and helpful regarding any modifications for my manuscript. And the editorial office were very helpful and supportive in contacting and monitoring with any update and offering help. It was my pleasure to contribute with your promising Journal and I am looking forward for more collaboration.

img

Mina Sherif Soliman Georgy

We would like to thank the Journal of Thoracic Disease and Cardiothoracic Surgery because of the services they provided us for our articles. The peer-review process was done in a very excellent time manner, and the opinions of the reviewers helped us to improve our manuscript further. The editorial office had an outstanding correspondence with us and guided us in many ways. During a hard time of the pandemic that is affecting every one of us tremendously, the editorial office helped us make everything easier for publishing scientific work. Hope for a more scientific relationship with your Journal.

img

Layla Shojaie

The peer-review process which consisted high quality queries on the paper. I did answer six reviewers’ questions and comments before the paper was accepted. The support from the editorial office is excellent.

img

Sing-yung Wu

Journal of Neuroscience and Neurological Surgery. I had the experience of publishing a research article recently. The whole process was simple from submission to publication. The reviewers made specific and valuable recommendations and corrections that improved the quality of my publication. I strongly recommend this Journal.

img

Orlando Villarreal

Dr. Katarzyna Byczkowska My testimonial covering: "The peer review process is quick and effective. The support from the editorial office is very professional and friendly. Quality of the Clinical Cardiology and Cardiovascular Interventions is scientific and publishes ground-breaking research on cardiology that is useful for other professionals in the field.

img

Katarzyna Byczkowska

Thank you most sincerely, with regard to the support you have given in relation to the reviewing process and the processing of my article entitled "Large Cell Neuroendocrine Carcinoma of The Prostate Gland: A Review and Update" for publication in your esteemed Journal, Journal of Cancer Research and Cellular Therapeutics". The editorial team has been very supportive.

img

Anthony Kodzo-Grey Venyo

Testimony of Journal of Clinical Otorhinolaryngology: work with your Reviews has been a educational and constructive experience. The editorial office were very helpful and supportive. It was a pleasure to contribute to your Journal.

img

Pedro Marques Gomes

Dr. Bernard Terkimbi Utoo, I am happy to publish my scientific work in Journal of Women Health Care and Issues (JWHCI). The manuscript submission was seamless and peer review process was top notch. I was amazed that 4 reviewers worked on the manuscript which made it a highly technical, standard and excellent quality paper. I appreciate the format and consideration for the APC as well as the speed of publication. It is my pleasure to continue with this scientific relationship with the esteem JWHCI.

img

Bernard Terkimbi Utoo

This is an acknowledgment for peer reviewers, editorial board of Journal of Clinical Research and Reports. They show a lot of consideration for us as publishers for our research article “Evaluation of the different factors associated with side effects of COVID-19 vaccination on medical students, Mutah university, Al-Karak, Jordan”, in a very professional and easy way. This journal is one of outstanding medical journal.

img

Prof Sherif W Mansour

Dear Hao Jiang, to Journal of Nutrition and Food Processing We greatly appreciate the efficient, professional and rapid processing of our paper by your team. If there is anything else we should do, please do not hesitate to let us know. On behalf of my co-authors, we would like to express our great appreciation to editor and reviewers.

img

Hao Jiang

As an author who has recently published in the journal "Brain and Neurological Disorders". I am delighted to provide a testimonial on the peer review process, editorial office support, and the overall quality of the journal. The peer review process at Brain and Neurological Disorders is rigorous and meticulous, ensuring that only high-quality, evidence-based research is published. The reviewers are experts in their fields, and their comments and suggestions were constructive and helped improve the quality of my manuscript. The review process was timely and efficient, with clear communication from the editorial office at each stage. The support from the editorial office was exceptional throughout the entire process. The editorial staff was responsive, professional, and always willing to help. They provided valuable guidance on formatting, structure, and ethical considerations, making the submission process seamless. Moreover, they kept me informed about the status of my manuscript and provided timely updates, which made the process less stressful. The journal Brain and Neurological Disorders is of the highest quality, with a strong focus on publishing cutting-edge research in the field of neurology. The articles published in this journal are well-researched, rigorously peer-reviewed, and written by experts in the field. The journal maintains high standards, ensuring that readers are provided with the most up-to-date and reliable information on brain and neurological disorders. In conclusion, I had a wonderful experience publishing in Brain and Neurological Disorders. The peer review process was thorough, the editorial office provided exceptional support, and the journal's quality is second to none. I would highly recommend this journal to any researcher working in the field of neurology and brain disorders.

img

Dr Shiming Tang

Dear Agrippa Hilda, Journal of Neuroscience and Neurological Surgery, Editorial Coordinator, I trust this message finds you well. I want to extend my appreciation for considering my article for publication in your esteemed journal. I am pleased to provide a testimonial regarding the peer review process and the support received from your editorial office. The peer review process for my paper was carried out in a highly professional and thorough manner. The feedback and comments provided by the authors were constructive and very useful in improving the quality of the manuscript. This rigorous assessment process undoubtedly contributes to the high standards maintained by your journal.

img

Raed Mualem

International Journal of Clinical Case Reports and Reviews. I strongly recommend to consider submitting your work to this high-quality journal. The support and availability of the Editorial staff is outstanding and the review process was both efficient and rigorous.

img

Andreas Filippaios

Thank you very much for publishing my Research Article titled “Comparing Treatment Outcome Of Allergic Rhinitis Patients After Using Fluticasone Nasal Spray And Nasal Douching" in the Journal of Clinical Otorhinolaryngology. As Medical Professionals we are immensely benefited from study of various informative Articles and Papers published in this high quality Journal. I look forward to enriching my knowledge by regular study of the Journal and contribute my future work in the field of ENT through the Journal for use by the medical fraternity. The support from the Editorial office was excellent and very prompt. I also welcome the comments received from the readers of my Research Article.

img

Dr Suramya Dhamija

Dear Erica Kelsey, Editorial Coordinator of Cancer Research and Cellular Therapeutics Our team is very satisfied with the processing of our paper by your journal. That was fast, efficient, rigorous, but without unnecessary complications. We appreciated the very short time between the submission of the paper and its publication on line on your site.

img

Bruno Chauffert

I am very glad to say that the peer review process is very successful and fast and support from the Editorial Office. Therefore, I would like to continue our scientific relationship for a long time. And I especially thank you for your kindly attention towards my article. Have a good day!

img

Baheci Selen

"We recently published an article entitled “Influence of beta-Cyclodextrins upon the Degradation of Carbofuran Derivatives under Alkaline Conditions" in the Journal of “Pesticides and Biofertilizers” to show that the cyclodextrins protect the carbamates increasing their half-life time in the presence of basic conditions This will be very helpful to understand carbofuran behaviour in the analytical, agro-environmental and food areas. We greatly appreciated the interaction with the editor and the editorial team; we were particularly well accompanied during the course of the revision process, since all various steps towards publication were short and without delay".

img

Jesus Simal-Gandara

I would like to express my gratitude towards you process of article review and submission. I found this to be very fair and expedient. Your follow up has been excellent. I have many publications in national and international journal and your process has been one of the best so far. Keep up the great work.

img

Douglas Miyazaki

We are grateful for this opportunity to provide a glowing recommendation to the Journal of Psychiatry and Psychotherapy. We found that the editorial team were very supportive, helpful, kept us abreast of timelines and over all very professional in nature. The peer review process was rigorous, efficient and constructive that really enhanced our article submission. The experience with this journal remains one of our best ever and we look forward to providing future submissions in the near future.

img

Dr Griffith

I am very pleased to serve as EBM of the journal, I hope many years of my experience in stem cells can help the journal from one way or another. As we know, stem cells hold great potential for regenerative medicine, which are mostly used to promote the repair response of diseased, dysfunctional or injured tissue using stem cells or their derivatives. I think Stem Cell Research and Therapeutics International is a great platform to publish and share the understanding towards the biology and translational or clinical application of stem cells.

img

Dr Tong Ming Liu

I would like to give my testimony in the support I have got by the peer review process and to support the editorial office where they were of asset to support young author like me to be encouraged to publish their work in your respected journal and globalize and share knowledge across the globe. I really give my great gratitude to your journal and the peer review including the editorial office.

img

Husain Taha Radhi

I am delighted to publish our manuscript entitled "A Perspective on Cocaine Induced Stroke - Its Mechanisms and Management" in the Journal of Neuroscience and Neurological Surgery. The peer review process, support from the editorial office, and quality of the journal are excellent. The manuscripts published are of high quality and of excellent scientific value. I recommend this journal very much to colleagues.

img

S Munshi

Dr.Tania Muñoz, My experience as researcher and author of a review article in The Journal Clinical Cardiology and Interventions has been very enriching and stimulating. The editorial team is excellent, performs its work with absolute responsibility and delivery. They are proactive, dynamic and receptive to all proposals. Supporting at all times the vast universe of authors who choose them as an option for publication. The team of review specialists, members of the editorial board, are brilliant professionals, with remarkable performance in medical research and scientific methodology. Together they form a frontline team that consolidates the JCCI as a magnificent option for the publication and review of high-level medical articles and broad collective interest. I am honored to be able to share my review article and open to receive all your comments.

img

Tania Munoz

“The peer review process of JPMHC is quick and effective. Authors are benefited by good and professional reviewers with huge experience in the field of psychology and mental health. The support from the editorial office is very professional. People to contact to are friendly and happy to help and assist any query authors might have. Quality of the Journal is scientific and publishes ground-breaking research on mental health that is useful for other professionals in the field”.

img

George Varvatsoulias

Dear editorial department: On behalf of our team, I hereby certify the reliability and superiority of the International Journal of Clinical Case Reports and Reviews in the peer review process, editorial support, and journal quality. Firstly, the peer review process of the International Journal of Clinical Case Reports and Reviews is rigorous, fair, transparent, fast, and of high quality. The editorial department invites experts from relevant fields as anonymous reviewers to review all submitted manuscripts. These experts have rich academic backgrounds and experience, and can accurately evaluate the academic quality, originality, and suitability of manuscripts. The editorial department is committed to ensuring the rigor of the peer review process, while also making every effort to ensure a fast review cycle to meet the needs of authors and the academic community. Secondly, the editorial team of the International Journal of Clinical Case Reports and Reviews is composed of a group of senior scholars and professionals with rich experience and professional knowledge in related fields. The editorial department is committed to assisting authors in improving their manuscripts, ensuring their academic accuracy, clarity, and completeness. Editors actively collaborate with authors, providing useful suggestions and feedback to promote the improvement and development of the manuscript. We believe that the support of the editorial department is one of the key factors in ensuring the quality of the journal. Finally, the International Journal of Clinical Case Reports and Reviews is renowned for its high- quality articles and strict academic standards. The editorial department is committed to publishing innovative and academically valuable research results to promote the development and progress of related fields. The International Journal of Clinical Case Reports and Reviews is reasonably priced and ensures excellent service and quality ratio, allowing authors to obtain high-level academic publishing opportunities in an affordable manner. I hereby solemnly declare that the International Journal of Clinical Case Reports and Reviews has a high level of credibility and superiority in terms of peer review process, editorial support, reasonable fees, and journal quality. Sincerely, Rui Tao.

img

Rui Tao

Clinical Cardiology and Cardiovascular Interventions I testity the covering of the peer review process, support from the editorial office, and quality of the journal.

img

Khurram Arshad